Ankylosing spondylitis (AS), with a prevalence of 0.15-1.8%1, is an under-recognized chronic disease which affects predominantly young men. A recent estimate of the US population concluded that there are approximately 2 million people with axial Spondylarthritis (SpA)2. The diagnosis of AS is made from a combination of clinical features1, and the presence of radiographic evidence of sacroiliitis which may be detected only after many years of inflammatory back pain. It is not uncommon for a delay of 5-10 years after the initial onset of symptoms before the diagnosis is made3,4. The availability of biomarkers would not only facilitate rapid diagnosis, but would also provide better assessment, prognosis and management of the disease.
The hallmark of AS is neo-ossification at the site of joint inflammation. Biologics involving TNF-α blockage are very effective for controlling joint inflammation. However, they have no major impact on structural damage and ankylosis progression in AS5. Novel agents targeting ankylosis are required to fundamentally alter the natural history of this debilitating disease.
Results from genetic studies, animal models and therapy involving TNF blockers suggest that the gut-joint axis plays a critical role in the pathogenesis of SpA6. For decades, a relationship between reactive arthritis (ReA) and certain enterobacteria (e.g. Salmonella, Yersinia, Shigella and Klebsiella) has been noted7. Some ReA patients eventually develop AS. The evidence for the association between AS and bacterial infections is controversial8,9.
There is an ongoing debate regarding whether inflammation and ankylosis in AS are linked events or independent processes10,11. Research on AS in humans subjects is limited by restricted access to target tissues, but animal studies can shed light on mechanisms involved in the joint ankylosing process. ank/ank (progressive ankylosis) mice represent an informative model for the study of joint ankylosis in AS due to similarities in the pattern of ankylosis (peripheral and axial) and aberrant Wnt-β-catenin signaling12,13. AS has long been viewed as a seronegative disease, notable for the absence of autoantibodies (autoabs). More recently, a reported protein microarray screening of patient plasma revealed multiple AS-specific IgG-autoabs directed against skeletal/connective tissue antigens14.